The existing health care system requires an individual to visit a health care facility to conduct point-in-time tests to monitor even the most basic healt status markers, which can miss fluctuations in body chemistries that are vital to accurate diagnoses, particularly in high-risk populations. Continuous multi-analyte health sensors have the potential to dramatically change health care by paving the way for decentralization of health care delivery and shifting the focus away from reactive treatment to preventative maintenance. PROFUSA, Inc. proposes to transform current biosensing paradigms by developing highly miniaturized, implantable, multi-analyte sensors composed of luminescent tissue integrating materials for continuous monitoring of body chemistries. The largest hurdle in developing implantable sensors is the foreign body response (FBR). Through the use of unique tissue integrating scaffolds, which are a major innovative improvement compared to current implantable sensors in that they induce capillary formation and in-growth rather than the typical FBR fibrous capsule formation, intimate access to metabolic markers and other analytes of interest is achieved. Analyte-specific luminescent sensing chemistries, are embedded in these hydrogel scaffolds. The resultant sensors are injected under the skin and monitored optically using a miniaturized, wireless, Band-Aid-like reader for continuous measurement or a hand-held wand for periodic self-measurement, depending on the clinical need. The proposed monitoring system is inconspicuously small and the form factor meets patient demands for widespread adoption of real-time, long-term monitoring body chemistries. Additionally, viewing of the collected data can be done remotely, allowing the physician access to medical data without the need for the patient to be present until a critical threshold is met. Past efforts by PROFUSA and collaborators have resulted in the successful development of prototype glucose sensors using this technology. Here, the development of a multi-analyte continuous monitor using the same platform is proposed with extended longevity. Glucose and creatinine are proposed to demonstrate the multi-analyte concept due to their importance as markers of food intake, metabolism and kidney function. Glucose and creatinine sensing nanospheres will be developed and optimized individually and incorporated into the tissue-integrating scaffolds to generate prototype sensors. Sensor longevity and accuracy will be enhanced to attain the desired 90-day functionality in vivo, with an ultimate goal of one year functionality. The development of PROFUSA's multi-analyte sensor platform, which has the potential for being customized to various disease states by integrating sensing nanospheres specific to analytes of interest, could potentially transform health care. Clinical adoption of a continuous multi-anlayte sensor will empower patients to take control of their own health, helping them to make decisions to maintain their health, while at the same time enabling physicians to more accurately reach a diagnosis and prescribe treatment.